Interaction between sodium and calcium ions in the process of transmitter release at the neuromuscular junction.

1. The interaction between Na and Ca ions on quantal transmitter release at the frog neuromuscular junction has been studied, using intracellular recording and averaging of responses.2. At low calcium concentrations, partial withdrawal of Na ions increases end-plate potential (e.p.p.) amplitudes and quantal content (m) and decreases the amplitude of the miniature e.p.p.s (m.e.p.p.s). Under these conditions the relation between [Ca] and m is highly non-linear. When plotted on double logarithmic co-ordinates withdrawal of [Na] causes a nearly parallel shift of this relation.3. Mutual interaction occurs between Ca, Na and Mg in transmitter release. With a constant low [Ca] in the medium, withdrawal of [Na] produces a smaller increase in m when [Mg] is high, than when [Mg] is low.4. In the presence of normal [Ca] (1.8 mM), [Na] withdrawal decreases the amplitude of the e.p.p. and produces a small decrease in m.5. The results can be explained by assuming that [Na] reduction has two mutually opposing effects on transmitter release: it makes more sites available for the action of Ca, and it lowers the amplitude of the action potential in the nerve terminals. The former effect dominates at low, the latter at high, calcium concentrations.